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Analysis: Reprogrammed cells open new medical window

This undated handout photo shows iPS cells derived from adult human dermal fibroblasts released by Kyoto University Professor Shinya Yamanak
This undated handout photo shows iPS cells derived from adult human dermal fibroblasts released by Kyoto University Professor Shinya Yamanak

By Ben Hirschler and Kate Kelland

LONDON (Reuters) - The Nobel Prize-winning discovery of how to reprogram ordinary cells to behave like embryonic stem cells offers a way to skirt around ethical problems with human embryos, but safety concerns make their future use in treating disease uncertain.

While researchers have already applied the scientific breakthroughs of Britain's John Gurdon and Japan's Shinya Yamanaka to study how diseases develop, making such cells into new treatments will involve a lot more checks.

Stem cells act as the body's master cells, providing the source material for all other cells. They could transform medicine by regenerating tissue for diseases ranging from blindness to Parkinson's disease.

Creating embryo-like stem cells without destroying embryos gets round a key controversy by avoiding the need to process embryos left over at fertility clinics - a system that has led to political objections in the United States and elsewhere.

Reprogrammed cells - known as induced pluripotent stem cells, or iPS cells - offer an ethically neutral alternative. They have been a source of intense research since Yamanaka discovered their potential in 2006, building on work that Gurdon did in frogs and tadpoles 40 years earlier.

SAFETY CONCERNS

Recently, however, different research groups have noticed problems with iPS cells, suggesting they may not be as good as embryonic ones. In one study, iPS cells died more quickly and another found multiple genetic mutations, raising concerns that they could cause tumors.

Despite this, Japanese researchers hope to test iPS cells in clinical trials for a form of blindness as early as next year - catching up with recent successful eye trials using embryonic stem cells.

Researchers in the West are generally more wary.

"There is a bit of a divergence between Japan and the rest of the world on this," Chris Mason, professor of regenerative medicine at University College London, told Reuters.

"Scientists in Japan are trying to move very rapidly towards clinical trials of iPS cells, whereas many of us still feel there are a lot of issues to overcome, especially in terms of safety."

The future potential for reprogrammed cells is that they could be taken from sick people who could have their own "person specific cell replacement" to mend damaged organs or tissues.

But key worries include the fact that iPS technology involves using genes which could also be tumor-inducing in some circumstances and that other as-yet undetected problems might crop up after the new cells have been put into patients.

Gurdon played down such worries and said regulatory authorities and governments should take a step back and let patients assess the potential benefits and risks for themselves.

"If you explain to a patient what can be done, and what might be the downside - then you should let the patient choose. Don't have ethicists or ... doctors or whoever say you may or may not have replacement cells," he told reporters.

DRUG DISCOVERY TOOL

Experts agreed that the pioneering work by the two new Nobel laureates had changed the field of stem cell research.

"What's grand in this discovery is that these specialized mature cells can rewind in their development and become stem cells," said Urban Lendahl, chairman of the Nobel awards committee.

Still, many experts believe the true promise of iPS cells is as unique research tools, rather than necessarily forming the basis of new medical therapies.

They have a key advantage over embryonic stem cells in that researchers can take them from people with a known disease, offering a window into how currently incurable illnesses develop at the cellular level.

Already, researchers have made iPS cells from patients with Gaucher's disease, Down Syndrome, Parkinson's and diabetes.

"I see iPS cells more for use in drug discovery and in understanding the mechanism of different diseases, rather than therapy," said Dusko Ilic, a senior lecturer in stem cell science at King's College London.

Traditionally, researchers have used stand-ins for human tissue such as yeast, flies or mice for their drug research. Now, they can use human cells containing a complete set of the genes that resulted in a particular disease.

(Additional reporting by Anna Ringstrom in Stockholm)

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